Science and Nature have papers that describe a version of the avian flu that …

When it infects humans, the avian flu is unusually lethal, killing over half the people who come down with symptoms. But, so far at least, the virus has only spread from birds to humans, and not between humans. Recently, some labs evolved a version of the avian flu that can be transmitted among ferrets while retaining its lethal nature. The researchers who did this work sequenced the flu genome, identified all the genetic changes, and sent publications in to Science and Nature.

That's where things got complicated, with the journals delaying publication and the National Science Advisory Board for Biosecurity stepping in. The end result was a moratorium on further research, with the journals discussing publishing a censored form of the original papers. During this pause, the World Health Organization convened its own panel of experts who released a statement on Friday, calling for the moratorium on new research to be extended, and saying that the papers should be published in full, even if that means an extensive delay.

The publication of the full details of the paper would allow anyone with a reasonable level of molecular biology skill to order up the requisite DNA and produce a copy of the newly evolved virus. That raises the risk that the virus could be spread by a lab that doesn't have the requisite containment expertise, or by someone who intentionally uses it as a weapon.

At the same time, the full sequence would also allow public health authorities to screen for the virus, and researchers to attempt to develop therapies that target it. Bruce Alberts, the Editor-in-Chief of Science, speaking at a press conference on Friday, suggested that knowing the sequence would allow research to determine their structure of the virus' proteins. All of this suggests there's value in a full publication.

Alberts spoke at a hastily organized press conference at the meeting of the American Association for the Advancement of Science. In general, he seemed annoyed that places like the WHO had let the issue slide for this long before it got dropped into his lap. "They could have worked on [a plan for publication] for the last five years and they did not," he said. "In fact, we were surprised and disappointed that nothing had been done until this so called 'emergency.'"

The complaint aside, it looks like Science will follow the WHO's advice; plans to publish a redacted version of the papers (which appeared certain just a few weeks ago), are now on hold. "The plan that we did have—both Nature and Science were on track to publish a redacted version in the middle of March—that's now not going to happen," Alberts said.

Ars was also given a statement from Dr. Philip Campbell, Editor-in-Chief of Nature. "Discussions at the WHO meeting made it clear how ineffective redaction and restricted distribution would be for the Nature paper," Campbell said. "It also underlined how beneficial publication of the full paper could be. So that is how we intend to proceed."

Both Alberts and Campbell emphasized that the research community will have to figure out how to ensure the publications are handled responsibly when they do come out. And, at the moment, nobody's even sure how to reach that sort of decision, much less when it will happen. For the time being, the papers look like they'll be stuck in limbo, perhaps the most famous papers that have never been published.

24 Reader Comments

People have said that physicists dealt with these kinds of restrictions and issues during the Cold War. Has there been any substantial input from veteran physicists on how to balance potentially dangerous information with the need for an open scientific process?

It does seem odd that places like the WHO, NIH, and CDC don't have a thoroughly vetted plan for handling the publication of research on potentially-dangerous infectious agents such as this. I would have thought it had happened decades ago.

Frankly, Science has a pretty significant stake in seeing such a plan put in place as well, so they can't really blame everyone else for failing to do so unless they've been sounding the alarm about this for years themselves.

Hmmm so we have DNA sequence for Smallpox and Polio widely available. What makes this different? Knee jerk reactions by bureaucrats fed to news organizations for sensations and hours of talk radio. Having it redacted doesn't make a difference the information is out. The stupid "got to do something" urge couldn't be overcome.

It does seem odd that places like the WHO, NIH, and CDC don't have a thoroughly vetted plan for handling the publication of research on potentially-dangerous infectious agents such as this. I would have thought it had happened decades ago.

Frankly, Science has a pretty significant stake in seeing such a plan put in place as well, so they can't really blame everyone else for failing to do so unless they've been sounding the alarm about this for years themselves.

"once the rockets are up, who cares where they come down?That's not my department", says Wernher von Braun (Tom Lehrer, "That Was the Year That Was/Wernher von Braun",1965.As nearly as I can tell, Science has always been about finding things out, and blind eye toward the uses that man might put that knowledge to. See Alfred Nobel et al. Is there research that just shouldn't be done? I have no answer for that... or for who should have the power and/or privileged of deciding it.

Seems like a gamble either way: release the info and someone might release it into the world; don't release the info and when someone else does find a way to sequence the avian flu virus in a deadly way, we don't have a defense for it.

I'm scared of the first option, but if I was a betting man, I'd pick it. The reason is because I think there are way more good people than bad people out there in the world and hopefully we can find an effective way to protect against it.

People have said that physicists dealt with these kinds of restrictions and issues during the Cold War. Has there been any substantial input from veteran physicists on how to balance potentially dangerous information with the need for an open scientific process?

I think it's a significantly different situation though WoC, and the altered costs and benefits naturally result in different methods being appropriate. Not to rewrite everything we discussed last time, but it seems there are a few main areas that would inform a decision. One involves how much of a threat there is without human involvement at all. The next involves the actual practicality of controlling both informational and technological spread. The last involves both the threat of spread and the value that can come from it.

If we imagine a cubic grid, with 3 axis covering "natural threat", "practicality of restriction", and "value of spread", nuclear technology would be about the most extreme lowest point example imaginable.

It is highly practical to restrict it. Nuclear research is immensely expensive, in time, economic cost and technological complexity. It involves entirely artificial elements or the extreme concentration of specific isotopes of elements that are themselves uncommon, tricky to work with, and vary by tiny fractions. It's nearly impossible to conceal development, which must take place over the course of years if not a decade or more, and it is truly impossible to conceal any sort of testing.

There is no even theoretical defense that could be developed, and thus little value in wide spread.

In contrast, pathogen research is practically the opposite on every measure.

There is every possibility that any strain we cause to evolve in a controlled setting may appear on its own in the wild. There are vast disease reservoirs and increasing surface area between them and human populations, which often simultaneously happen to be significantly more vulnerable then many due to malnutrition, poor access to clean water or basic sanitation, environmental destruction, etc. Even if we stopped nearly everything and hunkered down, it might just happen anyway.

It is highly impractical to restrict. The materials are the stuff of life itself, the most common and widely abundant elements in the world. The processes are doable with minimal equipment, which in turn is both ever falling in cost and has tremendous alternative uses (in turn creating a vast, turbulent market and making it very hard to track). The processes, model animals, and so forth are all impractical or impossible to restrict use of. It's very easy to conceal labs involved in research, and to conduct testing.

Merely knowing it's possible is probably enough for a small and sufficiently motivated group to make significant progress.

Countermeasures are quite feasible. There is every possibility of developing improved testing (which in turn can allow rapid early identification, quarantine and so forth), procedures, and vaccines or other treatments. This means there is significant positive value with having the research in the hands of as many professional researchers and institutions as possible.

The Cold War probably does have a certain number of lessons to teach, and I do share your interest in knowing what was done with weapons research in the past. But at the same time, I would also be cautious about exactly how much applicability those lessons would have. Even bio-weaponization research isn't at all in the same "dual use" class as something like this, and by the above tests could be much more reasonably restricted. It's a tough situation, but I lean towards a feeling that the best solution is one of active management and counter measures rather then passive information/technology control.

Good points. The materials and methods to make a superflu are much more readily available and less suspicious than the key ingredients amd facilities needed to make an A-bomb. But the situations and conditions associated with making a weaponized flu haven't changed from what they were before the news of these studies was published: anybody with the motivation could have tried the same thing, and the basic method isn't exactly a revolutionary approach to flu research. There's also far less chance of anybody making such a bio-weapon being able to ensure their own survival by making an effective vaccine against their flu. This puts them directly in harm's way regardless of where they intended to target for initial release, unlike setting off a nuke in a foreign country. It would be even less discriminating than bombing a market. And on the other hand, the chances of an A-bomb occurring in nature and threatening a city are next to nil, unlike a deadly new flu strain which seems inevitable, especially given the conditions that tend to develop them unintentionally.

But rather than making this another pro/con argument about publishing the full details of the studies I was really wondering what kind of practices that were used before could be applied here, since I didn't see anyone mention anything specific and there didn't seem to be any consultation in scientists or publishers with experience in restricted access research. I'd find it hard to believe that there isn't anything that can be taken from those experiences and used to help flesh out a policy on sensitive biomedical research.

My understanding of the case for full disclosure is that it may assist others in the production of an effective vaccine, as well as contributing to the general understanding of influenza.

Now, I have no beef with the latter, but as to the former, the trouble is, there is no reason to think that a vaccine based on the mutant stain would be any more effective than a vaccine based on the wild type, which really kills this argument stone dead. The whole point of this research was that it shows that H5N1 does not necessarily lose any virulence in mutating to a strain which passes easily between mammals. That's it. No one seriously thinks that the mutations they observed are the exact ones that would be selected in the wild, and that is critically important. In a publication, they can easily get across their point about the communicability and lethality and not say how the mutations were induced without losing any of the message.

Having said all that, any virologist worth their salt could probably guess roughly how they did it, and as I heard on BBC Radio 4 last week, as many as a hundred people already have full disclosure. So if you really want the literature, you could get it. The Streisand effect is in full swing now so that any measures which are taken to conceal the work will only be effective on future publications.

My understanding of the case for full disclosure is that it may assist others in the production of an effective vaccine, as well as contributing to the general understanding of influenza.

Actually, field testing and general detection (knowing sorts of things to look for in a newly observed strain) are at least as important, although perhaps you meant to include that a bit under "contributing to the general understanding of influenza."

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No one seriously thinks that the mutations they observed are the exact ones that would be selected in the wild, and that is critically important.

Really? Maybe not the exact ones, no doubt there would be a different mix. But usually there are only so many biological pathways to take, and the ones that are most energetically favorable are even more restricted. We see examples of convergent evolution all over the place, and it happens at the molecular level as well. Given similar environmental pressures, it would not be surprising if a strain evolved similar traits when it came to mammalian transmission.

You may be right, but I'd like to see some more support for your position. My reading lead to believe that the actual mutations developed were, all by themselves, of significant interest (and the process could be repeated by many independent labs with different ferrets to perhaps get a better handle on how many different ways there are and what sorts of mutations they involve). They could be integrated into tests and then watched for in any new wild strains. While not seeing any of them wouldn't necessarily give much info about risk level, the converse definitely would: if a wild strain did develop one of those mutations, it would definitely be worth paying a lot more attention to.

None of that helps with a vaccine, which as you say would likely need to be strain specific (other random mutations with nothing to do with transmission or lethality could nevertheless change surface antigens and the like). But sequencing detection and risk evaluation is critical, and there are a lot of measures public health officials (and the general public itself) can take even without any treatment in order to minimize spread.

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In a publication, they can easily get across their point about the communicability and lethality and not say how the mutations were induced without losing any of the message.

As I said, I think the specific mutations are part of the message, and it'd be good if many independent labs developed more and created a database of them as well. But I'd definitely be curious about arguments to the contrary.

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Having said all that, any virologist worth their salt could probably guess roughly how they did it,

Just "many generations of ferrets" is likely enough for better or worse. Doesn't sound like they used some special tool, but rather intelligent directed evolution. Any team with sufficient education (or the dedication to learn about it using the vast amount of freely available educational materials) could probably experiment and figure it out from there, although it might take many years.

Do they think there is a Dr Evil out there that will blackmail the world into 1 million....no 1 bazzillion dollars? It serves no purpose for anyone to release it. It takes a lot of equipment to make one, it is very dangerous, a lot of effort for what? Best evil course might be blackmail, I have the vaccine and will charge you X for it! Mwahhahaha, sent to a special island somewhere in the pacific? It is pretty silly. Not very well thought through "we gotta do something" reaction.

Having experience making vaccines with minor tweaks is a far greater benefit than the minor risk of a Dr Evil. If natural or otherwise were it to surface our current methods of containment will slow the vector enough and give enough time to work out a vaccine, before any apocalyptic number of deaths. To put restrictions on this type of research only makes it so we are unprepared when it does happen. These tools are available to researchers, it's not going to be a Timothy McVeigh who wants revolution that will be able to make this virus.

The fact is that even if they publish this data, it would be no harder or easier to construct than any other deadly virus with a known sequence (smallpox, etc). And how would you construct such a virus? Order some damn oligos, and piece it together. This actually came up during a debate a while back over whether or not to destroy all stocks of polio once the virus is eradicated, and a virologist (can't recall his name) ordered up oligos and constructed polio virus to demonstrate the futility of destroying research stocks as well (this was actually a paper in Science, don't remember when). Since then, companies which produce oligos will BLAST whatever sequence you're ordering, and you cannot order such oligos anymore without special authorization. So even if the full sequence is publish, for someone to do something nefarious with the sequence they would need to construct their own oligos which is by no means trivial, and very, very unlikely to happen.

My understanding of the case for full disclosure is that it may assist others in the production of an effective vaccine, as well as contributing to the general understanding of influenza.

Actually, field testing and general detection (knowing sorts of things to look for in a newly observed strain) are at least as important, although perhaps you meant to include that a bit under "contributing to the general understanding of influenza."

Yeah, I considered this under the same heading, but perhaps I should have been more specific.

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No one seriously thinks that the mutations they observed are the exact ones that would be selected in the wild, and that is critically important.

Really? Maybe not the exact ones, no doubt there would be a different mix. But usually there are only so many biological pathways to take, and the ones that are most energetically favorable are even more restricted. We see examples of convergent evolution all over the place, and it happens at the molecular level as well. Given similar environmental pressures, it would not be surprising if a strain evolved similar traits when it came to mammalian transmission.

I realise it’s partially (or even mainly) an argument from incredulity, but I would personally be stunned if the same mutations were responsible for the natural jump to inter-human transmission as were found in this experimental ferret study. I take your point about convergent evolution, but I, for one, think it more likely that a wild virus discovered to have several of the new mutations would turn out to have been released from a lab – deliberately or otherwise.

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You may be right, but I'd like to see some more support for your position.

I’m not sure what that support would look like – evidence of a negative. On the other side, is there any evidence that mutations induced in evolutionary experiments in labs produce the same gene changes as are found in the wild? As far as I know, the orthomyxoviridae are particularly difficult to predict in drift mode.

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My reading lead to believe that the actual mutations developed were, all by themselves, of significant interest (and the process could be repeated by many independent labs with different ferrets to perhaps get a better handle on how many different ways there are and what sorts of mutations they involve). They could be integrated into tests and then watched for in any new wild strains. While not seeing any of them wouldn't necessarily give much info about risk level, the converse definitely would: if a wild strain did develop one of those mutations, it would definitely be worth paying a lot more attention to.

I hadn’t thought of this, and it’s a very good point. If the same experiment in many different labs produce the same mutations or a small set of mutations then that would be significant as it implies that the virus is constrained in how it may evolve mammalian transmissibility – well, in ferrets at least. That possibility alone could make dissemination of the information worthwhile (and I’m not at all against that anyway).

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As I said, I think the specific mutations are part of the message, and it'd be good if many independent labs developed more and created a database of them as well. But I'd definitely be curious about arguments to the contrary.

I’m coming round to this way of thinking myself (as Oscar Wilde said, Arguments are to be avoided; they are always vulgar and often persuasive). I really wonder if this experiment has ever been done – do viruses evolve new abilities along predictable genetic lines (nylonase accepted)?

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Having said all that, any virologist worth their salt could probably guess roughly how they did it,

Just "many generations of ferrets" is likely enough for better or worse. Doesn't sound like they used some special tool, but rather intelligent directed evolution. Any team with sufficient education (or the dedication to learn about it using the vast amount of freely available educational materials) could probably experiment and figure it out from there, although it might take many years.

It’s irritating that it’s as easy as this, but I’m sure you’re right. That said, the world must be a safer place than our governments seem determined to convince us if it’s this easy to begin an apocalyptic contagion and no one has bothered to do it. Yet.

The problem is that significant numbers of people already have the results. Some of the researchers have presented their findings in conferences. They've emailed each other. They've communicated with their scientific communities. So regardless of what anyone may want, the cat is well and truly out of the bag.

The other problem is that of knowing something can be done. Once you know that a goal is achievable, you're already half-way to achieving it. I'll use another analogy this time - the genie's out of the bottle.

You can try to suppress the results, which means trying to stop scientists from talking, or from working in particular areas of research. Alternatively, you can focus on those areas of research, with the aim of developing a cure before a naughty person develops the disease. I know which approach I'd bet my life on.

If the cat is out the bag the surprise about this should be less obvious as it to be in the same line publishing stem cell research and this case of sequenced genome to be research.this science.doesn't fair well today it could take decade's to fully understand it so well the weight in how WHO put it its should be published.

(PS logging in took 3 clicks two directing me to Itunes the third finally where i should be >:|)

The reason is because I think there are way more good people than bad people out there in the world and hopefully we can find an effective way to protect against it.

The problem is ratios mean nothing in the real world. As long as you have just one person/nation out there with the money and the means to do this having a 1,000,0000 good people out there means exactly jack.

And yes if you can't tell I have ZERO faith in humanity. We are a self destructive species.

Do they think there is a Dr Evil out there that will blackmail the world into 1 million....no 1 bazzillion dollars? It serves no purpose for anyone to release it. It takes a lot of equipment to make one, it is very dangerous, a lot of effort for what?

Really? You think that? I think a quote from the Dark Knight sums things up the best.

"Because some men aren't looking for anything logical, like money. They can't be bought, bullied, reasoned, or negotiated with. Some men just want to watch the world burn." -Alfred Pennyworth

If you don't think there are people out there who are willing to sacrifice the world as long as the US gets "what's coming to them". I'd like you to go ahead and look up some propaganda on how we are the great evil. Funny thing about true zealots, especially the religious ones, they aren't overly rational.

Hmmm so we have DNA sequence for Smallpox and Polio widely available. What makes this different? Knee jerk reactions by bureaucrats fed to news organizations for sensations and hours of talk radio. Having it redacted doesn't make a difference the information is out. The stupid "got to do something" urge couldn't be overcome.

I'm responding to this post, but I could easily be replying to the other post that mentioned Smallpox, etc.

The reason why this is different from Smallpox and Polio is that we have vaccines and tests for those diseases already.If someone made those up in a lab, it would be less of an issue to get a vaccine/quarantine/treatment plan together.

Also, I don't know enough about the details of how it is done, but my guess would be that it's easier to take the existing avian flu and modify it this way than to create something entirely in the lab. (Again, that could be completely wrong, but it's what makes sense to me)

I'm not advocating that this needs to be held back (this argument makes sense either way), just pointing out that it is definitely different from those other diseases.